Genetic linkage of affective disorders (AD) to c-Harvey-ras-1 (HRAS 1) and in insulin (INS) genes on chromosome 11 was examined using three pedigrees with bipolar illness. Our results indicate the absence of linkage from 0 to 15% recombination which contrasts with the finding of another group who found linkage to these markers in a large Old Order Amish pedigree. The reason for this discrepancy is not clear. Conceivably these contrasting findings favor etiological heterogeneity in AD. Linkage to the color-blindness region, Xq28, was found to be absent in these same pedigrees using the St14 probe. New restriction fragment polymorphisms (RFLP's) were detected at the gene regions encoding the gastrin releasing peptide (GRP), substance P, muscarinic receptor M-1, muscarinic receptor, M-4 and beta-adrenergic receptor. Analysis of the linkage relationships between AD and these genes are in progress. New full length calmodulin cDNa for both human and rat have been isolated and sequenced. The nucleotide structures of these cDNAs are substantially different from those that have been reported. These results provide evidence for the presence of at least two actively transcribed calmodulin genes in these species. A cDNA clone specific for the 87 kDa substrate of protein kinase C (PKCS-87) has been isolated from a rat brain expression library using a polyclonal antibody.